Submissions for variant NM_001018115.3(FANCD2):c.2605+1G>A

gnomAD frequency: 0.00003  dbSNP: rs142365855

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000255506	SCV000321626	uncertain significance	not provided	2019-08-08	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in an in-frame deletion of a critical region; This variant is associated with the following publications: (PMID: 26633542)
Baylor Genetics	RCV001332747	SCV001525154	likely pathogenic	Fanconi anemia complementation group D2	2019-07-31	criteria provided, single submitter	clinical testing	This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Revvity Omics, Revvity	RCV001332747	SCV002022344	pathogenic	Fanconi anemia complementation group D2	2019-01-11	criteria provided, single submitter	clinical testing
Invitae	RCV001855003	SCV002317618	likely pathogenic	Fanconi anemia	2024-01-18	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 27 of the FANCD2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCD2 are known to be pathogenic (PMID: 17436244). This variant is present in population databases (rs142365855, gnomAD 0.007%). Disruption of this splice site has been observed in individual(s) with clinical features of Fanconi anemia (PMID: 26633542, 34327028). ClinVar contains an entry for this variant (Variation ID: 265138). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Daryl Scott Lab, Baylor College of Medicine	RCV001332747	SCV004102668	pathogenic	Fanconi anemia complementation group D2	2023-11-10	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001332747	SCV004806334	pathogenic	Fanconi anemia complementation group D2	2024-03-25	criteria provided, single submitter	clinical testing